The present invention relates to methods of solubilizing metal salts of pyridine-2-thiol-1-oxide, to such solubilized salts, and to compositions containing the solubilized salts. Such products are particularly useful as microbiocides in the cosmetic, pharmaceutical and textile treatment arts.
Metal salts of pyridine-2-thiol-1-oxide (often referred to as "pyrithione") are described in detail in U.S. Pat. No. 2,809,971. As there discussed, the metal salts are conveniently prepared by reaction of a soluble metal compound with a soluble salt of pyrithione, such as an alkali metal salt or ammonium salt. On combination of these reactants, the metal salt precipitates and is recovered. Metal salts in the present specification particularly include salts like those disclosed in said U.S. Pat. No. 2,809,971, i.e., salts in which the metal group is inter alia, copper, iron, manganese, tin, mercury, cobalt, chromium, lead, gold, cadmium, nickel, silver, zinc, titanium, arsenic, antimony, zirconium, or bismuth. As in the aforementioned patent, the term "metal" as employed in the present specification includes elements of metallic character such as arsenic, characterized in the patent as "semi-metals" and also ammonium salts.
The salts of pyrithione are useful as fungicides and bactericides, and certain of them are particularly adaptable to topical application to the skin. The zinc salt specifically is quite effective as an agent against seborrhea, and has found wide acceptance in the cosmetic art for use in soaps, shampoos, hairdressings, and the like.
One disadvantage of the metal salts of pyrithione, such as the zinc salt, is their insolubility in common solvents. The zinc salt, for example, is substantially insoluble in water (10-20 p.p.m.), ethanol (310 p.p.m.) benzene (3-5 p.p.m.), petroleum oils, and most common organic solvents. The material is slightly more soluble in chloroform (3400 p.p.m.), dimethyl formamide (8100 p.p.m.) and dimethyl sulfoxide (5.13 percent). Accordingly, it has been found difficult to formulate suitable cosmetic and other compositions containing these heavy metal salts in dissolved form. The few solvents known for the salts are unacceptable for cosmetic uses and the salts must always be present in such compositions in dispersed form, necessarily rendering the compositions opaque. Although there are soluble salts or pyrithione, such as the alkali metal salts, these soluble salts are thought to be toxic and unacceptable for use at active levels in cosmetic or dermatologic compositions for topical application to the skin.
U.S. Pat. No. 3,636,213 discloses the solubilization of metal salts of pyrithione in common organic solvents and/or water by combination with an amine and also including an aqueous or ethanolic solution of an acid, generally a physiologically acceptable acid. The patent discloses compositions having pH's of from about 8.5 to 9.0.
U.S. Pat. Nos. 3,940,482 and 3,785,985 as well as the article "Clear Zinc Pyrithione Preparations" by T. Gerstein in the Journal of the Society of Cosmetic Chemistry, vol 23, p. 99-114 (Feb 1972) all disclose solubilization of metal pyrithiones by combination with an amine.
It is known that heavy metal pyrithione solubility is increased in an alkaline media. For example, the zinc salt is soluble in water at pH 7 to an extent of about 10 to 20 parts per million. This is raised to a value of 35 to 50 parts per million at a pH of 8. U.S. Pat. No. 3,636,213 teaches that the solubility of the zinc salt according to that invention, in a composition having a pH of about 8, can be as high as at least 200 parts per million or higher.
Current state of the art limits the practical use of soluble salts of pyridine-2-thiol-1-oxide in aqueous systems to a pH of about 8.5 and higher. This dramatically hampers the use of such salts in the art of designing modern hair- and skin-applied products. Those skilled in such cosmetic and pharmaceutical arts readily acknowledge the importance of maintaining a product pH matched closely to that of the intended substrate, namely, the skin. Skin is a biological organ and its character may, therefore, vary extensively from person to person. Its pH may also vary as well although its range is generally recognized as 4.0 to 7.5. The acidic environment has several advantages but perhaps the primary function is the control of harmful microbes on the surface to avoid infection. The topical application of a hair or skin care product that inherently has an alkaline character may, among other things, cause a disruption of this "acid mantle" of the skin thereby potentially compromising its function.
Accordingly it is a purpose of the instant invention to provide a solubilized pyrithione salt for cosmetic applications such as hair and skin treating compositions which have a pH between about 4.0 and 7.4.